LEPTIN: A DRIVING FORCE BEHIND THYROID PROBLEMS

IJCRR Section: Healthcare Sci. Journal Impact Factor 4.016 LEPTIN: A DRIVING FORCE BEHIND THYROID PROBLEMS Singla Gesu 1, Bedi GK 2, Sandhu HS 3, Vij Chittranjan 4 Research Article 1 MD (Biochemistry), Assistant Professor, Department of Biochemistry, AIMSR, Bathinda; 2 MD (Biochemistry), Professor & Head, Department of Biochemistry, GMC, Patiala; 3 MD (Medicine), Professor & Head, Department of Medicine, GMC, Patiala; 4 MD (Biochemistry), Professor & Head, Department of Biochemistry, MMU, Solan. ABSTRACT Introduction: Apart from diabetes mellitus, thyroid dysfunction is one of the most common endocrine disorders encountered in adults, affecting up to 10% of the UK population Leptin is a 16kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. Aim: The aim of this study was to estimate thyroid hormones and Serum Leptin levels in patients with thyroid disorders and to find their correlation with each other. Material & Methods: 50 diagnosed patients of thyroid disorders and 30 healthy controls were recruited in our study. Serum Leptin, Serum T 3, TSH levels were estimated in both cases and controls using ELISA method. Results: There was significant negative correlation between Serum Leptin and Serum T 3. There was no significant but negative correlation between Serum Leptin and Serum T 4. A very significant positive correlation was seen between Serum TSH and Serum Leptin levels. Conclusion: Leptin problems are a driving force behind thyroid problems. Leptin triggers the decreased production of thyroid hormones. Improving leptin problems and losing weight will improve thyroid function. Key Words: Leptin, Thyroid, TSH- Thyroid Stimulating Hormone, T4- Thyroxine, T3- Triiodothyronine INTRODUCTION Thyroid dysfunction is one of the most common endocrine disorders encountered in adults. The two most common thyroid diseases are inadequate thyroid function i.e. hypothyroidism & excessive thyroid function i.e. hyperthyroidism. [1] Thyroid hormones are essential for the regulation of important processes involved in thermogenesis, energy consumption & many other metabolic reactions. Leptin, the ob gene product is a peptide hormone, secreted by adipocytes. [2] It circulates at levels proportional to body fat. Leptin enters the central nervous system in proportion to plasma concentration. It controls food intake and energy expenditure by acting on receptors in mediobasal hypothalamus. [3] In human, leptin concentrations are elevated in the obese when compared with lean subjects, and their levels are positively correlated to the degree of obesity. In addition administration of leptin to rats deprived of food corrected many of the neuroendocrine changes (e.g. the decrease in the release of thyroid hormone) that occur as a result of food deprivation. [4] There are three general ways in which alterations of the leptin regulatory loop could lead to obesity. a) Failure to produce leptin as occur in ob/ob mice, would result in obesity b) inappropriately low leptin secretion for a given fat mass c) Obesity could result from relative or absolute insensitivity to leptin at its site of action. [5] Both thyroid hormones and leptin have effects on similar aspects of body homeostasis, but their potential interaction is controversial. [2] Aims and Objectives 1. To study the serum leptin levels in various disorders of thyroid gland. 2. To evaluate thyroid hormone levels in various disorders of thyroid gland. 3. To study the correlation of serum leptin with thyroid hormones in various disorders of thyroid gland. Corresponding Author: Gesu Singla, Assistant Professor, Department of Biochemistry, AIMSR, Bathinda. Contact No: 84270-07271; E-mail: gesu.singla88@gmail.com Received: 22.12.2015 Revised: 25.01.2016 Accepted: 27.02.2016 Int J Cur Res Rev Vol 8 Issue 9 May 2016 48

MATERIALS AND METHODS The present study was conducted in Department of Biochemistry at Govt. Medical College, Patiala on 50 diagnosed cases of thyroid disorder referred by Department of Medicine, Rajindra Hospital, Patiala from October, 2011 to May, 2012. For comparison 30 age and gender matched healthy individuals constituted the control group. Patients with history of any drug intake, history of any infection/illness, pregnant females, diabetic patients, cancer including thyroid cancer were excluded from the study. Informed consent of all subjects and detailed history were taken at the beginning of the study. Fasting venous blood samples were collected under all aseptic conditions, and subsequently, Serum Leptin, Serum T 3, TSH levels were estimated in both cases and controls. Serum Leptin, Serum T 3, TSH were estimated by ELISA method. ERBA-thyrokit was used for Serum.T 3, T 4 and TSH whereas AviBion Human Leptin ELISA Kit [6] was used for Serum Leptin. Although the patients were known cases of thyroid disorders but when their hormonal status was assessed they were divided into 3 categories: euthyroid, hypothyroid and hyperthyroid. Out of the 50 cases, 20 cases were of euthyroidism, 20 cases were of hypothyroidism and 10 cases were of hyperthyroidism. Statistical Analysis Statistical analysis was performed using Statistical Package for Social Sciences (SPSS).Means and Standard Deviations (SD) were calculated for all parameters. The independent sample t-test was used to compare the means of different variables in the two groups. In addition, the Pearson correlation coefficient (r) was used for correlation analysis. P value <0.05 was considered significant. RESULTS The mean age in the present study was 42.2±15.30 years (Table I). There were 40 females and 10 males and male: female ratio was 1:4(Table II). Although the patients were known cases of thyroid disorders but when their hormonal status was assessed they were divided into 3 categories: euthyroid, hypothyroid and hyperthyroid. Out of the 50 cases, 20 cases were of euthyroidism, 20 cases were of hypothyroidism and 10 cases were of hyperthyroidism (Table IV). Serum T 3, TSH and Serum Leptin was measured in both study and control group and their correlation was studied with statistical analysis (Table III,V). There was significant negative correlation between Serum Leptin and Serum T 3 (Table VI).There was insignificant but negative correlation between Serum Leptin and Serum T 4 (Table VI). There was a statistically very significant positive correlation between Serum Leptin and Serum TSH (Table VI). There were total 20 (40%) cases of euthyroidism out of total 50(100%) cases. Among those 20(40%) cases, 12(60%) were having normal leptin levels, 6(30%) cases were having increased leptin levels and 2(10%) cases were having decreased leptin levels. In total 20 (40%) cases of hypothyroidism, 4(20%) were having normal leptin levels, 14(70%) cases were having increased leptin levels and 2(10%) cases were having decreased leptin levels. In total 10 (10%) cases of hyperthyroidism cases, 2(20%) cases were having normal leptin levels and 8(80%) cases were having decreased leptin levels (Table VII). DISCUSSION Mean age for the study group was 42.2±15.30years and for control group was 36.07±14.24 years. There was no significant difference in the mean age of patients among the two groups. Yoshida et al observed the mean age of 38.4±1.8 years in his study. [10] Tene Perez et al found the mean age of 35 years in his study. [11] In this study there were 40 females and 10 males and male: female ratio was 1:4. Zimmermann Belsing et al had a similar type of sex distribution among his patients i.e. 2 males and 8 females.[9] In the present study, there was significant (p=0.026) but negative correlation (r=-0.314) between Serum Leptin and Serum T 3. Al-shoumer et al gave significant (p=0.003) negative correlation between Serum Leptin and Serum T 3. [4] Azza M Abdu Allah also reported negative correlation between Serum Leptin and Serum T 3 with significant p value (p=0.000). [12]The possible reason for significant p value between Serum Leptin and Serum T 3 may be that the T 3 induced alternation in adipocyte sensitivity to catecholamines can give rise to altered serum leptin levels (decreased in hyper thyroid patients).[7] There was no significant but negative correlation between Serum Leptin and Serum T 4. A study by Ozata et al supported the present study and gave the negative but insignificant correlation between Serum Leptin and SerumT 4. [13] Hseih et al reported significant negative correlation between Serum Leptin and Serum T 4. [14] The reason is that leptin affects thyroid deiodinase activities with activation of T 4 to T 3 conversion. [8,9] There was positive and very significant correlation between Serum Leptin and Serum TSH levels. Iacobellis et al gave the positive correlation between Serum Leptin and Serum TSH with significant p value (p=0.01). [15] Siemienska et al shows the positive correlation between S. Leptin and S. TSH with significant p value (p<0.01).[16] Azza M. Abdu Allah et al did a similar study and gave positive correlation 49 Int J Cur Res Rev Vol 8 Issue 9 May 2016

between Serum Leptin and Serum TSH with significant p value (p<0.01).[12] The reason for significant correlation between Serum Leptin and Serum TSH is because TSH receptors have been identified in adipose tissues and therefore we cannot deny the possibility that TSH might directly regulate leptin gene expression. [7] CONCLUSION The present study shows that Serum Leptin levels were raised in most of the hypothyroid patients and decreased in majority of hyperthyroid patients suggesting that leptin triggers the decreased production of thyroid hormones. Leptin problems are a driving force behind thyroid problems. Problems in the leptin are often the primary cause of many hypothyroid symptoms in overweight individuals. There is relationship between leptin and thyroid gland probably via an influence of leptin on negative feedback of thyroid hormones as well as influence on thermogenesis. Improving leptin problems and losing weight will improve thyroid function. But surely a larger study group is required to prove this relationship. REFERENCES 1. Constanti A, Bartke A, Khardori R. The Thyroid Gland. In: Taylor and Francis. Basic Endocrinology for Students of Pharmacy and Allied Health Sciences. Harwood Academic Publishers 4 th edn.singapore: 2005;59-61. 2. Baig M, Karira KA, Ahmed A, Zaidi P, Niaz K, Kamal S. Serum Leptin level in Hyperthyroid Female Patients. Journal of Pakistan Medical Association. 2003;53(5):176-81. 3. Williams KW, Scott MM, Elmquist JK. From observation to experimentation: leptin action in the mediobasal hypothalamus. Am. J. Clin. Nutr. 2009;89(3):985S 990S. 4. Al-Shoumer KA, Vasanthy BA, Makhlouf HA, Al-Zaid MM. Leptin levels in Arabs with primary hyperthyroidism. Ann Saudi Med. 2000;20(2):113-8. 5. Friedman JM and Halaas JL. Leptin and the regulation of body weight in mammals. Nature Macmillan Publishers Ltd 1998;395:766. 6. AviBion Human Leptin ELISA Kit, User Manual. Available at:http://www.anibiotech.fi/anibiotech/pdfs/orgenium-leptin_ User Manual Rev1.09.pdf 7. Janson A, Karlsson FA, Micha-Johansson G, Bolme P, Brönnegård M, Marcus C. Effects of stimulatory and inhibitory thyrotropin receptor antibodies on lipolysis in infant adipocytes. J Clin Endocrinol Metab. 1995;80(5):1712-1712. 8. Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol 2010;316:165-171. 9. Zimmermann-Belsing T, Brabant G, Holst JJ, Feldt-Rasmussen U. Circulating leptin and thyroid dysfunction. Eur J Endocrinol. 2003;149(4):257-71. 10. Yoshida T, Momotani N, Hayashi M, Monkawa T, Ito K, Saruta T. Serum leptin concentrations in patients with thyroid disorders. Clin Endocrinol (Oxf). 1998;48(3):299-302. 11. Tene Pérez CE, Revilla-Monsalve MC, Amato D, Escobedo de la Peña J, Galván R, Millán-Guerrero RO. Correlation between serum leptin levels and insulin sensitivity in diffuse toxic goiter. Endocr Res. 2004;30(1):19-27. 12. Azza M. Abdu-Allah, Riham G. Mahfouz, Seham A. Khodeer, Walid A. Shehab-Eldin, Mostafa El Nagar. Study of Resistin and Leptin in patients with Thyroid Dysfunction. Journal of American Science, 2011;7(3):569-76. 13. Ozata M, Ozisik G, Bingol N, Corakci A, Gundogan MA. The effects of thyroid status on plasma leptin levels in women. J Endocrinol Invest. 1998;21(6):337-41. 14. Hsieh CJ, Wang PW, Wang ST, Liu RT, Tung SC, Chien WY et al. Serum leptin concentrations of patients with sequential thyroid function changes. Clin Endocrinol (Oxf) 2002;57(1):29-34. 15. Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F. Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol (Oxf). 2005;62(4):487-91. 16. Siemińska L, Wojciechowska C, Kos-Kudła B, Marek B, Kajdaniuk D, Nowak M et al. Serum concentrations of leptin, adiponectin, and interleukin-6 in postmenopausal women with Hashimoto s thyroiditis. Endokrynol Pol. 2010;61(1):112-6. Table I: Comparison of age distribution of study and control group Age (in years) Study group Control group P value Mean±SD 42.2±15.30 36.07±14.24 0.0789 Table II : Distribution of study and control group according to sex Sex Study Group Control Group Number of cases %age Number of cases %age Male 10 20 7 13 Female 40 80 23 77 Total 50 100 30 100 Int J Cur Res Rev Vol 8 Issue 9 May 2016 50

Table III: Comparison of Serum T3, T4 and TSH in study group and control group Hormone Group Number of patients Range Mean ±SD P value Serum T3 Study 50 0.1-4.6 0.99±0.73 0.651 Control 30 0.5-2.0 1.05±0.41 Serum T4 Study 50 3.76-19.8 8.5±3.34 0.011 Control 30 4.1-9.3 6.85±1.20 Serum TSH Study 50 0.09-44.6 5.88±8.74 0.0321 Control 30 0.6-4.2 2.38±1.04 Table IV: Distribution of Serum T 3 and TSH in the study group on the basis of their hormonal status Hormone Hormonal Status Range Mean±SD Euthyroidism 0.1-2.59 1.44±1.82 S. T 3 (ng/ml) S. T 4 (µg/dl) S. TSH (μiu/ml) Hypothyroidism 0.1-1.9 0.71±0.43 Hyperthyroidism 0.1-4.6 1.41±1.22 Euthyroidism 6.7-13.5 8.62-1.77 Hypothyroidism 3.76-13.56 7.24±3.10 Hyperthyroidism 4.52-19.56 10.75±4.63 Euthyroidism 0.6-3.09 2.02±1.80 Hypothyroidism 3.9-44.6 12.93±10.42 Hyperthyroidism 0.09-0.41 0.25±0.10 Table V: Comparison of Serum Leptin in study and control group Hormone Group Number of patients Range Mean ± SD P value Serum Leptin(pg/ml) Study 50 744-29280 8078.1±6054.3 0.786 Control 30 1600-14600 7741.6±3929.47 Table VI: Correlation between Serum Leptin and Serum T3, T4 and TSH in study and control group Correlation Group r P value Serum Leptin and Serum T3 Study -0.314* 0.026 Control -0.148 0.435 Serum Leptin and Serum T4 Study -0.251* 0.078 Control 0.048 0.801 Serum Leptin and Serum TSH Study 0.416* 0.0027 Control 0.081 0.67 51 Int J Cur Res Rev Vol 8 Issue 9 May 2016

Table VII: Leptin levels in study group on the basis of their hormonal status Hormonal Status T3 T4 TSH Total Cases Normal Leptin Increased Leptin Decreased Leptin Number % age Number % age Number % age Number % age Euthyroidism N N N 20 40 12 60 6 30 2 10 Hypothyroidism 20 40 4 20 14 70 2 10 Hyperthyroidism 10 20 2 20 - - 8 80 Total 50 100 18 100 20 100 12 100 N = Normal, = increase, = decrease Int J Cur Res Rev Vol 8 Issue 9 May 2016 52